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The association of gastric cancer risk with plasma folate, cobalamin, and methylenetetrahydrofolate reductase polymorphisms in the European Prospective Investigation into Cancer and Nutrition.

Abstract

Previous studies have shown inconsistent associations of folate intake and polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene with gastric cancer risk. Our nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort is the first prospective study of blood folate levels and gastric cancer. Gastric cancer cases (n=247) and controls (n=631) were matched for study center, age, sex, and time of blood donation. Two common single nucleotide polymorphisms of the MTHFR gene were determined, as were plasma concentrations of folate, cobalamin (vitamin B12), total homocysteine, and methylmalonic acid (cobalamin deficiency marker) in prediagnostic plasma. Risk measures were calculated with conditional logistic regression. Although no relations were observed between plasma folate or total homocysteine concentrations and gastric cancer, we observed a trend toward lower risk of gastric cancer with increasing cobalamin concentrations (odds ratio, 0.79 per SD increase in cobalamin; P=0.01). Further analyses showed that the inverse association between cobalamin and gastric cancer was confined to cancer cases with low pepsinogen A levels (marker of severe chronic atrophic gastritis) at the time of blood sampling. The 677 C-->T MTHFR polymorphism was not associated with gastric cancer, but we observed an increased risk with the variant genotype of the 1298 A-->C polymorphism (odds ratio, 1.47 for CC versus AA; P=0.04). In conclusion, we found no evidence of a role of folate in gastric cancer etiology. However, we observed increased gastric cancer risk at low cobalamin levels that was most likely due to compromised cobalamin status in atrophic gastritis preceding gastric cancer.

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    ,

    LOCUS for Homocysteine and Related Vitamins, Institute of Medicine, University of Bergen, Bergen, Norway. vollset@uib.no

    , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,

    Source

    MeSH

    Adult
    Aged
    Case-Control Studies
    Cohort Studies
    Europe
    Female
    Folic Acid
    Gastritis, Atrophic
    Homocysteine
    Humans
    Male
    Methylenetetrahydrofolate Reductase (NADPH2)
    Methylmalonic Acid
    Middle Aged
    Polymorphism, Single Nucleotide
    Prospective Studies
    Risk Factors
    Stomach Neoplasms
    Vitamin B 12

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    18006931

    Citation

    Vollset, Stein Emil, et al. "The Association of Gastric Cancer Risk With Plasma Folate, Cobalamin, and Methylenetetrahydrofolate Reductase Polymorphisms in the European Prospective Investigation Into Cancer and Nutrition." Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, vol. 16, no. 11, 2007, pp. 2416-24.
    Vollset SE, Igland J, Jenab M, et al. The association of gastric cancer risk with plasma folate, cobalamin, and methylenetetrahydrofolate reductase polymorphisms in the European Prospective Investigation into Cancer and Nutrition. Cancer Epidemiol Biomarkers Prev. 2007;16(11):2416-24.
    Vollset, S. E., Igland, J., Jenab, M., Fredriksen, A., Meyer, K., Eussen, S., ... González, C. A. (2007). The association of gastric cancer risk with plasma folate, cobalamin, and methylenetetrahydrofolate reductase polymorphisms in the European Prospective Investigation into Cancer and Nutrition. Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, 16(11), pp. 2416-24.
    Vollset SE, et al. The Association of Gastric Cancer Risk With Plasma Folate, Cobalamin, and Methylenetetrahydrofolate Reductase Polymorphisms in the European Prospective Investigation Into Cancer and Nutrition. Cancer Epidemiol Biomarkers Prev. 2007;16(11):2416-24. PubMed PMID: 18006931.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - The association of gastric cancer risk with plasma folate, cobalamin, and methylenetetrahydrofolate reductase polymorphisms in the European Prospective Investigation into Cancer and Nutrition. AU - Vollset,Stein Emil, AU - Igland,Jannicke, AU - Jenab,Mazda, AU - Fredriksen,Ase, AU - Meyer,Klaus, AU - Eussen,Simone, AU - Gjessing,Håkon K, AU - Ueland,Per Magne, AU - Pera,Guillem, AU - Sala,Núria, AU - Agudo,Antonio, AU - Capella,Gabriel, AU - Del Giudice,Giuseppe, AU - Palli,Domenico, AU - Boeing,Heiner, AU - Weikert,Cornelia, AU - Bueno-de-Mesquita,H Bas, AU - Carneiro,Fátima, AU - Pala,Valeria, AU - Vineis,Paolo, AU - Tumino,Rosario, AU - Panico,Salvatore, AU - Berglund,Göran, AU - Manjer,Jonas, AU - Stenling,Roger, AU - Hallmans,Göran, AU - Martínez,Carmen, AU - Dorronsoro,Miren, AU - Barricarte,Aurelio, AU - Navarro,Carmen, AU - Quirós,José R, AU - Allen,Naomi, AU - Key,Timothy J, AU - Bingham,Sheila, AU - Linseisen,Jakob, AU - Kaaks,Rudolf, AU - Overvad,Kim, AU - Tjønneland,Anne, AU - Büchner,Frederike L, AU - Peeters,Petra H M, AU - Numans,Mattijs E, AU - Clavel-Chapelon,Françoise, AU - Boutron-Ruault,Marie-Christine, AU - Trichopoulou,Antonia, AU - Lund,Eiliv, AU - Slimani,Nadia, AU - Ferrari,Pietro, AU - Riboli,Elio, AU - González,Carlos A, PY - 2007/11/17/pubmed PY - 2008/5/17/medline PY - 2007/11/17/entrez SP - 2416 EP - 24 JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology JO - Cancer Epidemiol. Biomarkers Prev. VL - 16 IS - 11 N2 - Previous studies have shown inconsistent associations of folate intake and polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene with gastric cancer risk. Our nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort is the first prospective study of blood folate levels and gastric cancer. Gastric cancer cases (n=247) and controls (n=631) were matched for study center, age, sex, and time of blood donation. Two common single nucleotide polymorphisms of the MTHFR gene were determined, as were plasma concentrations of folate, cobalamin (vitamin B12), total homocysteine, and methylmalonic acid (cobalamin deficiency marker) in prediagnostic plasma. Risk measures were calculated with conditional logistic regression. Although no relations were observed between plasma folate or total homocysteine concentrations and gastric cancer, we observed a trend toward lower risk of gastric cancer with increasing cobalamin concentrations (odds ratio, 0.79 per SD increase in cobalamin; P=0.01). Further analyses showed that the inverse association between cobalamin and gastric cancer was confined to cancer cases with low pepsinogen A levels (marker of severe chronic atrophic gastritis) at the time of blood sampling. The 677 C-->T MTHFR polymorphism was not associated with gastric cancer, but we observed an increased risk with the variant genotype of the 1298 A-->C polymorphism (odds ratio, 1.47 for CC versus AA; P=0.04). In conclusion, we found no evidence of a role of folate in gastric cancer etiology. However, we observed increased gastric cancer risk at low cobalamin levels that was most likely due to compromised cobalamin status in atrophic gastritis preceding gastric cancer. SN - 1055-9965 UR - https://www.unboundmedicine.com/medline/citation/18006931/The_association_of_gastric_cancer_risk_with_plasma_folate_cobalamin_and_methylenetetrahydrofolate_reductase_polymorphisms_in_the_European_Prospective_Investigation_into_Cancer_and_Nutrition_ L2 - http://cebp.aacrjournals.org/cgi/pmidlookup?view=long&pmid=18006931 DB - PRIME DP - Unbound Medicine ER -